Arroyo C M, Schafer R J, Kurt E M, Broomfield C A, Carmichael A J
US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, USA.
J Appl Toxicol. 2000 Dec;20 Suppl 1:S63-72. doi: 10.1002/1099-1263(200012)20:1+<::aid-jat687>3.0.co;2-b.
Cytokines play a major role in both acute and chronic inflammatory processes, including those produced by sulfur mustard (2,2'-dichlorodiethyl sulfide, HD). This study describes responses of normal human epidermal keratinocytes (NHEK) to HD, defined by interleukin-1beta (IL-1beta), IL-6, IL-8 and tumor necrosis factor alpha (TNF-alpha) release. Commercially available enzyme-linked immunosorbent assay (ELISA) kits were used to measure the cytokine release in NHEK during exposure to 100 and 300 microM of HD. Exposure to 100 microM HD increased the release of cytokines. The amounts of IL-8 and TNF-alpha present in cell suspensions increased up to 59-fold and 4-fold, respectively, above control levels when NHEK were exposed to 300 microM HD. Exposure of NHEK to 300 microM HD had a highly variable effect on the release of IL-1beta, where sometimes the secretion of IL-1beta increased above baseline level and at other times it decreased in cell suspensions. Supernatants were collected from cell culture flasks 24 h after exposure of 100 and 300 microM HD and significantly increased levels of IL-6 were observed. Interleukin-6 was released in a concentration-dependent manner, 3.6-fold up to 8.4-fold, respectively, in supernatant. These pro-inflammatory mediators IL-1beta, IL-8, TNF-alpha and IL-6 may play an important role in HD injury. The present findings suggest that the cytokine changes detected could be used as potential biomarkers of cutaneous vesicant injury.
细胞因子在急性和慢性炎症过程中都起着重要作用，包括由硫芥（2,2'-二氯二乙硫醚，HD）产生的炎症过程。本研究描述了正常人表皮角质形成细胞（NHEK）对HD的反应，以白细胞介素-1β（IL-1β）、IL-6、IL-8和肿瘤坏死因子α（TNF-α）的释放来定义。使用市售的酶联免疫吸附测定（ELISA）试剂盒来测量NHEK在暴露于100和300微摩尔HD期间的细胞因子释放。暴露于100微摩尔HD会增加细胞因子的释放。当NHEK暴露于300微摩尔HD时，细胞悬液中IL-8和TNF-α的含量分别比对照水平增加了59倍和4倍。NHEK暴露于300微摩尔HD对IL-1β的释放有高度可变的影响，有时IL-1β的分泌高于基线水平，而在其他时候细胞悬液中的分泌则减少。在暴露于100和300微摩尔HD 24小时后，从细胞培养瓶中收集上清液，观察到IL-6水平显著升高。IL-6以上清液中浓度依赖性方式释放，分别为3.6倍至8.4倍。这些促炎介质IL-1β、IL-8、TNF-α和IL-6可能在HD损伤中起重要作用。目前的研究结果表明，检测到的细胞因子变化可作为皮肤糜烂性损伤的潜在生物标志物。
